DOCSLIB.ORG

Transport of Molecules in the Tumor Interstitium: a Review1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Transport of Molecules in the Tumor Interstitium: a Review1 [CANCER RESEARCH 47. 3039-3051. June 15, 1987] Review Transport of Molecules in the Tumor Interstitium: A Review1 Rakesh K. Jain Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213-3890 Abstract these two spaces. We have recently summarized our work on blood flow and exchange in the tumor vascular subcompartment The transport of fluid and solute molecules in the interstitium is elsewhere (8, 9). In what follows we will discuss our own governed by the biological and physicochemical properties of the inter findings on the interstitial transport in tumors as well as those stitial compartment as well as the physicochemical properties of the test molecule. The composition of the interstitial compartment of neoplastic of others. tissues is significantly different from that of most normal tissues. In The transport of a solute or a fluid molecule in the intersti general the tumor interstitial compartment is characterized by large tium is governed by the physiological (e.g., pressure) and phys interstitial space, high collagen concentration, low proteoglycan and icochemical properties (e.g., size, charge, structure, composi hyaluronate concentrations, high interstitial fluid pressure and flow, tion) of the interstitial subcompartment as well as physicochem absence of anatomically well-defined functioning lymphatic network, high ical properties of the test molecule. These properties have been effective interstitial diffusion coefficient of macromolecules, as well as recently reviewed for normal tissues by several authors (10-15). large hydraulic conductivity and interstitial convection compared to most In this article we will discuss the tumor interstitial properties normal tissues. While these factors favor movement of macromolecules in the following order: volume, structure, and composition of in the tumor interstitium, high interstitial pressure and low microvascular the interstitial space (Section II); pressure-flow relationship in pressure may retard extravasation of molecules and cells, especially in large tumors. These differences in transport parameters have major the interstitium (Section III); and interstitial transport param implications in tumor growth and métastases,as well as in tumor detection eters (Section IV). For each parameter, we will outline the and treatment. methods of measurement, discuss the key results, and finally point out the implications for tumor growth, detection, and I. Introduction treatment. Most normal and neoplastic tissues can be divided into three subcompartments: vascular, interstitial, and cellular. In addi II. Volume, Structure, and Composition of the Tumor Interstitial tion, most normal tissues also contain lymphatic channels in Space the interstitial compartment. Once a molecule used for cancer The interstitial subcompartment of a tumor is bounded by detection or treatment is injected into the blood stream, it encounters the following "resistances" before reaching the in- the walls of blood vessels on one side and by the membranes of cells on the other. In normal tissues, the blood vessels are tracellular space: (a) distribution through vascular space; (b) surrounded by a basement membrane, which may be damaged transport across microvascular wall; (c) transport through in or missing in tumors (for review see, e.g., Ref. 8). In addition, terstitial space; and (</) transport across cell membrane. Each the anatomically well-defined functioning lymphatic vessels of these transport processes may involve both convection and present in normal tissues may be absent in solid tumors (16). diffusion. In addition, in each of these subcompartments the [Note that a tumor may invade and hence incorporate lymphatic molecule may (a) be metabolized and undergo degradation, (b) vessels of the host tissue.] Similar to normal tissues, the inter bind nonspecifically to proteins or other components, or (c) stitial space of tumors is composed predominantly of a collagen bind specifically to the target element(s) (e.g., an enzyme, an and elastic fiber network. Interdispersed within this cross-linked antigen) involved in growth, detection, or treatment (1-4). structure are the interstitial fluid and macromolecular constit Most investigators to date have focused their research on uents (hyaluronate and proteoglycans) which form a hydrophilic understanding the biochemistry, biophysics, and molecular bi gel. It is sometimes convenient to divide the interstitial space ology of cancer cells with limited attention paid to the in vivo into two compartments: the colic ;d-rich gel space containing interstitial environment they exist in. The advent of hybridoma the hydrophilic hyaluronate and proteoglycans; and the colloid- technology and genetic engineering has led to large scale pro poor free-fluid space. In this paper, we will discuss quantitative duction of monoclonal antibodies and other biologically useful results on the volume and composition of each of these spaces. molecules. If these molecules are to be used clinically, methods must be developed to deliver them selectively to the target cells in vivo (5-7). Since no molecule can reach the tumor cells from A. Volume of Interstitial Space blood without passing through the vascular and interstitial subcompartments, it seems reasonable to find out more about The volume of the interstitial space is usually obtained by the structure and function of these two subcompartments. We subtracting vascular space from the extracellular space. Vascu have focused our research in the past few years on the experi lar space is measured by a marker confined to blood vessels, mental and mathematical characterization of transport through and the extracellular space is measured by a marker excluded by cells. In a limited number of studies, these spaces have been Received 10/7/86; revised 3/9/87; accepted 3/20/87. measured morphometrically. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in Shown in Table 1 are the data of Cullino et al. (17) for accordance with 18 U.S.C. Section 1734 solely to indicate this fact. various carcinomas and a sarcoma. These investigators used 1This article is based on research supported by grants from the National sodium, chlorine, or D-mannitol as an extracellular marker and Cancer Institute, the National Science Foundation, and the Richard K. Mellon Foundation and by an NIH Research Career Development Award (1980-1985) dextran 500 (M, ~375,000) as a vascular marker. [Note that and a Guggenheim Fellowship (1983-1984). dextran 500 may overestimate the vascular space due to some 3039 Downloaded from cancerres.aacrjournals.org on September 29, 2021. © 1987 American Association for Cancer Research. INTERSTITIAL TRANSPORT IN TUMORS Table I Interstitial spaces of tumors vascular permeability in tumors and/or selective affinity of injected substances for tumor cells. HostRatHumanTumorFibrosarcoma (%)52.6space 4956VV256 4.3°36.3± carcinomaH5123 2.8"43.3± B. Collagen and Elastic Fiber Content carcinomaH3683 1.1"50.6± 3.5°54.6± carcinomaNovikofT Histological examination of tissues using appropriate stains hepatomaNormal 4.4°20.5± liverGastrocnemius 0.6°15.6± demonstrates the presence of collagenous and elastic fibers. The muscleDS-carcinosarcomaSarcoma-MSarcoma-BSkeletal±0.7°38»40eSff13C60 basic structural unit of the collagenous fibers is the collagen molecule. The main body of this protein molecule has a cylin drical structure (diameter, ~ 1.5 nm; length, ~300 nm; molec muscleFibrosarcoma ular weight, ~285,000) and is composed of 3 peptidic a chains A-MCFibrosarcoma ±555 (molecular weight, ~95,000) coiled in a rope-like fashion to C-MCFibrosarcoma I3314± BP-IIMuscleSkinLungKidneyGliomasMeningiomasNormal form a triple helix. Depending upon the composition of the a ±234 chains, the collagen molecules can be divided into at least 10 ±329 ±834±620-40*13-15»6-7*Ref.1718192021types; each type has similar structure and size (23). While the collagen fibers offer considerable tensile strength along their length, elastic fibers provide the rubber-like elasticity to a tissue. The structural units of elastic fibers are the microfibrillar pro brainInterstitial tein and elastin. The physical and mechanical properties of ' Interstitial space: mean ±SD; tumor weight, ~2-15 g; sodium, chlorine, or elastic fibers depend on their amino acid composition (14, IS, i>nKinniicilas extracellular marker and dextran 500 as vascular marker. * Extracellular space; morphometric analysis. 23). *Extracellular space; tracer, "Cr-EDTA; measurement made ~50 min postin Collagen is usually measured by tissue content of hydroxy- jection. proline, since it is assumed that this amino acid occurs almost exclusively in the scleroproteins of the connective tissue (24). Collagen content of nine hepatomas, W256 carcinoma, R-2788 extravasation (8).] The interstitial space of tumors in general is lymphosarcoma, and two fibrosarcomas in rats and two hepa very large, and that of hepatomas is more than twice that of the tomas in mice was measured by Cullino et al. (24-26). All host liver. Similar results were obtained by Rauen et al. (18), Appelgren et al. (19), and O'Connor and Bale (20) in various hepatomas contained more collagen than liver did (Table 2). Unlike regenerating liver, collagen content per unit tissue sarcomas and by Bakay (21) in human brain tumors (Table 1). weight remained constant during growth in eight of nine rat Although
Load more

Recommended publications
  • Understanding IDIOPATHIC PULMONARY FIBROSIS (IPF)
    Understanding IDIOPATHIC PULMONARY FIBROSIS (IPF) An educational health series from National Jewish Health National Jewish Health Our Mission since 1899 is to heal, to discover, and to educate as a preeminent healthcare institution. We serve by providing the best integrated and innovative care for patients and their families; by understanding and finding cures for the diseases we research; and by educating and training the next generation of healthcare professionals to be leaders in medicine and science. njhealth.org Understanding IDIOPATHIC PULMONARY FIBROSIS (IPF) An educational health series from National Jewish Health® In this Issue What is Idiopathic Pulmonary Fibrosis or IPF? 2 Living a Full Life With IPF 6 Healthy Lifestyle 8 Treatment of IPF 12 Avoiding Infections 13 Medications 14 Oxygen Therapy 15 Breathing Techniques 17 Lung Transplant 18 Action Plan for IPF 19 Living a Full Life at Any Stage of IPF 21 Stage 1 22 Stage 2 26 Stage 3 29 Stage 4 31 Note: This information is provided to you as an educational service of National Jewish Health. It is not meant as a substitute for your own doctor. © Copyright 2017, National Jewish Health Materials were developed through a partnership between National Jewish Health and PVI, PeerView Institute for Medical Education. What is Idiopathic Pulmonary Fibrosis or IPF? What is Idiopathic Pulmonary Fibrosis or IPF? Interstitial lung disease (ILD) is a broad category of lung diseases that includes more than 200 disorders that can be characterized by fibrosis (scarring) and/or inflammation of the lungs. Despite an exhaustive evaluation, in many people the cause of ILD remains unknown.
    [Show full text]
  • A Role of Inflammation and Immunity in Essential Hypertension—Modeled and Analyzed Using Petri Nets
    International Journal of Molecular Sciences Article A Role of Inflammation and Immunity in Essential Hypertension—Modeled and Analyzed Using Petri Nets Dorota Formanowicz 1 , Agnieszka Rybarczyk 2,3 , Marcin Radom 2,3 and Piotr Formanowicz 2,3,* 1 Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, 60-806 Poznan, Poland; [email protected] 2 Institute of Computing Science, Poznan University of Technology, 60-965 Poznan, Poland; [email protected] (A.R.); [email protected] (M.R.) 3 Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland * Correspondence: [email protected] Received: 15 April 2020; Accepted: 5 May 2020; Published: 9 May 2020 Abstract: Recent studies have shown that the innate and adaptive immune system, together with low-grade inflammation, may play an important role in essential hypertension. In this work, to verify the importance of selected factors for the development of essential hypertension, we created a Petri net-based model and analyzed it. The analysis was based mainly on t-invariants, knockouts of selected fragments of the net and its simulations. The blockade of the renin-angiotensin (RAA) system revealed that the most significant effect on the emergence of essential hypertension has RAA activation. This blockade affects: (1) the formation of angiotensin II, (2) inflammatory process (by influencing C-reactive protein (CRP)), (3) the initiation of blood coagulation, (4) bradykinin generation via the kallikrein-kinin system, (5) activation of lymphocytes in hypertension, (6) the participation of TNF alpha in the activation of the acute phase response, and (7) activation of NADPH oxidase—a key enzyme of oxidative stress.
    [Show full text]
  • Interstitial Lung Disease (ILD) Is a Broad Category of Lung Diseases That Includes More Than 130 Disorders Which Are Characterized by Scarring (I.E
    Interstitial Lung Disease Interstitial lung disease (ILD) is a broad category of lung diseases that includes more than 130 disorders which are characterized by scarring (i.e. “fibrosis”) and/or inflammation of the lungs. ILD accounts for 15 percent of the cases seen by pulmonologists (lung specialists). In ILD, the tissue in the lungs becomes inflamed and/or scarred. The interstitium of the lung refers to the area in and around the small blood vessels and alveoli (air sacs). This is where the exchange of oxygen and carbon dioxide take place. Inflammation and scarring of the interstitium disrupts this tissue. This leads to a decrease in the ability of the lungs to extract oxygen from the air. There are different types of interstitial lung disease that fall under the category of ILD. Some of the common ones are listed below: Idiopathic (unknown) Pulmonary Fibrosis Connective tissue or autoimmune disease-related ILD Hypersensitivity Pneumonitis Wegener’s Granulomatosis Churg Strauss (vasculitis) Chronic Eosinophilic Pneumonia Eosinophilic granuloma (Langerhan’s cell histoiocytosis) Drug Induced Lung Disease Sarcoidosis Bronchiolitis Obliterans Lymphangioleiomyomatosis The progression of ILD varies from disease to disease and from person to person. It is important to determine the specific form of ILD in each person because what happens over time and the treatment may differ depending on the cause.. Each person responds differently to treatment, so it is important for your doctor to monitor your treatment. What are Common Symptoms of ILD? The most common symptoms of ILD are shortness of breath with exercise and a non- productive cough. These symptoms are generally slowly progressive, although rapid worsening can also occur.
    [Show full text]
  • Interstitial Fluid Lung Disease (IFLD) of the Interstitium Organ the Cause and Self-Care to a Self-Cure for Lung Disease
    ISSN: 2476-2377 Review Article International Journal of Cancer Research & Therapy Interstitial Fluid Lung Disease (IFLD) of the Interstitium Organ the Cause and Self-Care to a Self-Cure for Lung Disease * 1 2 Corresponding author Robert O Young *, Galina Migalko * Robert O Young, Naturopathic Practitioner and nutritionist, Department of alternative 1Naturopathic Practitioner, biochemist and nutritionist, Department medicine and the alkaline diet, 16390 Dia del Sol, Valley Center, California 92082, of alternative medicine and the alkaline diet, Valley Center, California, USA. USA Galina Migalko, Medical Doctor, Naturopathic Medical Doctor, Universal Medical Imagining Center, 12410 Burbank Blvd. Valley Village, California 91607, USA. 2Medical Doctor and Naturopathic Medical Doctor, Universal Medical Imaging Center, Valley Village, California, USA Submitted: 19 Dec 2019; Accepted: 20 Jan 2020; Published: 31 Jan 2020 Abstract Interstitial lung disease (IFLD), or diffuse parenchymal lung disease (DPLD), is a group of lung diseases affecting the Interstitium (the interstitial fluids or space around the alveoli (air sacs of the lungs) [1,2]. Micrograph of usual interstitial pneumonia (UIP). UIP is the It concerns alveolar epithelium, pulmonary capillary endothelium, most common pattern of interstitial pneumonia (a type of basement membrane, and perivascular and perilymphatic tissues. It interstitial lung disease) and usually represents pulmonary occurs when metabolic, dietary, respiratory and environmental acids fibrosis caused by decompensated acidosis of the interstitial injure the lung tissues that triggers an abnormal healing response. fluids of the largest organ of the human body - the Interstitium. Ordinarily, the body generates just the right amount of tissue to repair H&E stain. Autopsy specimen. acid damage, but in interstitial lung disease, the repair process goes awry because of the acidic pH (ideal healing takes place at a pH of This makes it more difficult for oxygen to pass into the bloodstream.
    [Show full text]
  • Exchange of Macromolecules Between Plasma and Skin Interstitium in Extensive Skin Disease
    0022-202X/ 81/ 7606-0489$02.00/ 0 THE JOU RN AL OF INV ESTIGATIVE DERMATOLOGY, 76:489-492, 1981 Vol. 76, No.6 CopyrighL © 198 1 by The Williams & Wilkins Co. Printed in U.S.A. Exchange of Macromolecules between Plasma and Skin Interstitium in Extensive Skin Disease ANNE-MARIE WORM, M.D. Departments of Clinical Physiology and Dermatology, The Finsen Institute, Cop enhagen, Denmarll The concentrations of albumin, transferrin, IgG and in all cases and 12r'I_IgG in case no 1-5}. Inulin (Laevosan Gesellschaft, 0:' 2-macroglobulin were measured in serum (C.) and in Linz, Austria) in a 10% solu tion was used for determination of the extracellular fluid volume by the single-shot technique [9]. blister fluid (Cb ) from lesional skin obtained by suction in 11 patients with extensive skin disease. The results Procedure -w-ere compared with those of 10 matched control sub­ Each study was carried out in the morning after at least 12 hl' of jects. In the patients the Cb/CH ratios and the distribution ratios (i.e., intravascular to total masses) of the 4 pro­ fasting and 30 min of rest in the supine position to stabilize lymph fl ow and extracellular body fluid volumes. Weighed amounts of about 8 ).lei teins and that of inulin were correlated to the corre­ of each radioiodine labeled protein and 40 ml of inulin were injected sponding molecular weights. The distribution ratios of into one arm vein. Venous blood samples were drawn wi th a syringe the proteins were calculated from plasma volume (PV), and without stasis from the other arm once before and 14 times dUJ'ing C ", C b and extracellular fluid volume (ECV) determined the next 180 min after injection at specified intervals.
    [Show full text]
  • Meconium Aspiration Syndrome: a Narrative Review
    children Review Meconium Aspiration Syndrome: A Narrative Review Chiara Monfredini 1, Francesco Cavallin 2 , Paolo Ernesto Villani 1, Giuseppe Paterlini 1 , Benedetta Allais 1 and Daniele Trevisanuto 3,* 1 Neonatal Intensive Care Unit, Department of Mother and Child Health, Fondazione Poliambulanza, 25124 Brescia, Italy; [email protected] (C.M.); [email protected] (P.E.V.); [email protected] (G.P.); [email protected] (B.A.) 2 Independent Statistician, 36020 Solagna, Italy; [email protected] 3 Department of Woman and Child Health, University of Padova, 35128 Padova, Italy * Correspondence: [email protected] Abstract: Meconium aspiration syndrome is a clinical condition characterized by respiratory failure occurring in neonates born through meconium-stained amniotic fluid. Worldwide, the incidence has declined in developed countries thanks to improved obstetric practices and perinatal care while challenges persist in developing countries. Despite the improved survival rate over the last decades, long-term morbidity among survivors remains a major concern. Since the 1960s, relevant changes have occurred in the perinatal and postnatal management of such patients but the most appropriate approach is still a matter of debate. This review offers an updated overview of the epidemiology, etiopathogenesis, diagnosis, management and prognosis of infants with meconium aspiration syndrome. Keywords: infant newborn; meconium aspiration syndrome; meconium-stained amniotic fluid Citation: Monfredini, C.; Cavallin, F.; Villani, P.E.; Paterlini, G.; Allais, B.; Trevisanuto, D. Meconium Aspiration 1. Definition of Meconium Aspiration Syndrome Syndrome: A Narrative Review. Meconium aspiration syndrome (MAS) is a clinical condition characterized by respira- Children 2021, 8, 230. https:// tory failure occurring in neonates born through meconium-stained amniotic fluid whose doi.org/10.3390/children8030230 symptoms cannot be otherwise explained and with typical radiological characteristics [1].
    [Show full text]
  • The Immune System and Kidney Disease: Basic Concepts and Clinical Implications
    REVIEWS The immune system and kidney disease: basic concepts and clinical implications Christian Kurts1, Ulf Panzer2, Hans-Joachim Anders3 and Andrew J. Rees4 Abstract | The kidneys are frequently targeted by pathogenic immune responses against renal autoantigens or by local manifestations of systemic autoimmunity. Recent studies in rodent models and humans have uncovered several underlying mechanisms that can be used to explain the previously enigmatic immunopathology of many kidney diseases. These mechanisms include kidney-specific damage-associated molecular patterns that cause sterile inflammation, the crosstalk between renal dendritic cells and T cells, the development of kidney-targeting autoantibodies and molecular mimicry with microbial pathogens. Conversely, kidney failure affects general immunity, causing intestinal barrier dysfunction, systemic inflammation and immunodeficiency that contribute to the morbidity and mortality of patients with kidney disease. In this Review, we summarize the recent findings regarding the interactions between the kidneys and the immune system. Considerable progress has been made both in under- role of the cellular immune responses that drive renal 1Institutes of Molecular standing the basic immune mechanisms of kidney disease. Moreover, we summarize recent discoveries Medicine and Experimental disease and in translating these findings to clinical about complement- and antibody-mediated nephritis, Immunology (IMMEI), therapies. Sophisticated animal studies combined and we discuss kidney pathologies that are mediated Rheinische Friedrich- with the analysis of clinical samples have led to a pre- by renal autoantigen-specific antibodies, especially those Wilhelms-Universität, cise knowledge of the autoimmune targets and of the that are induced by crossreactive microorganism-specific Sigmund-Freud-Str. 25, 53105 Bonn, Germany. mechanisms responsible for kidney injury.
    [Show full text]
  • Anti-Inflammatory Drugs in the Treatment of Meconium Aspiration Syndrome
    ACTA MEDICA MARTINIANA 2011 SUPPL. 1 DOI: 10.2478/v10201-011-0007-7 15 ANTI-INFLAMMATORY DRUGS IN THE TREATMENT OF MECONIUM ASPIRATION SYNDROME Mokra D.1, Mokry J.2, Calkovska A.1 1Department of Physiology, 2Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic Abstract Meconium aspiration syndrome (MAS) is a major cause of respiratory distress in both the term and post- term neonates. Obstruction of the airways, dysfunction of pulmonary surfactant, inflammation, lung edema, pulmonary vasoconstriction and bronchoconstriction participate in the pathogenesis of this disorder. Since the inflammatory changes associated with meconium aspiration cause a severe impairment of the lung parenchyma including surfactant and influence the reactivity of both vascular and airway smooth muscle, administration of anti-inflammatory drugs may be of benefit also in the management of MAS. This article reviews effects of various anti-inflammatory drugs used in experimental models of MAS as well as in the treatment of newborns with meconium aspiration. Key words: meconium aspiration syndrome, inflammation, anti-inflammatory drugs, newborn, animal model Meconium aspiration syndrome (MAS) MAS is a serious disease in both the term and post-term newborns. Obstruction of the airways by aspirated meconium with subsequent alveolar atelectasis behind the plug and air-trapping, inactivation of pulmonary surfactant, inflammation, edema, pulmo- nary vasoconstriction are often leading to persistent pulmonary hypertension (PPHN), and bronchoconstriction participate in the pathogenesis of MAS (Figure 1). Because meconium-induced inflammation with its multiple impacts on the lungs plays more im- portant role than was previously thought, various anti-inflammatory drugs have been tested in the treatment of MAS.
    [Show full text]
  • Immune Recognition and Response to the Renal Interstitium
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 31(1991), pp. 518—530 Immune recognition and response to the renal interstitium CAROLYN J. KELLY, DAVID A. ROTH, and CATHERINE M. MEYERS Renal-Electrolyte Section, University of Pennsylvania, Philadelphia, Pennsylvania, USA Advances in cellular and molecular immunology over the paststricted localization, or it may not be visible because it has not decade have revolutionized the way we think about interactionsbeen processed in such a way to be recognizable to T cells. T between the immune system and parenchymal tissues. Thecells recognize peptide fragments of antigen in association with availability of well characterized experimental models of organ-either class II (CD4 cells) or class I (CD8 cells) major specific or systemic autoimmunity has allowed advances inhistocompatibility complex (MHC) antigens [13—151. Cells basic immunology to be incorporated into understanding thewhich present antigen to class 11-restricted CD4 T cells are basis for deviant immune responses resulting in host injury, asthought to endocytose the antigen, digest it within lysosomes, well as the mechanisms of tolerance to organ-specific antigensand re-express peptide fragments of the antigen associated with [1—5]. This review outlines a framework analysis for under-class II MHC [16, 171. This antigen-MHC association probably standing how the immune system interacts with the interstitialoccurs in a peptide "groove" in the class II antigen [181, as has compartment of the kidney. This framework is comprised ofbeen demonstrated to exist on class I by crystallographic four sections.
    [Show full text]
  • The Effect of Meconium and Amniotic Fluid on Alveolar Macrophage Function
    THE EFFECT OF MECONIUM AND AMNIOTIC FLUID ON ALVEOLAR MACROPHAGE FUNCTION A Thesis Submitted to the Graduate Faculty in Partial Fulfillment of the Requirements for the Degree of Master of Science in the Department of Pathology and Microbiology Faculty of Veterinary Medicine University of Prince Edward Island Sylvia J. Craig Charlottetown, P.E.I. June, 2003 © 2003. S. Craig Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. National Library Bibliothèque nationale 1^1 of Canada du Canada Acquisitions and Acquisisitons et Bibliographic Services services bibliographiques 395 Wellington Street 395, rue Wellington Ottawa ON K1A0N4 Ottawa ON K1A 0N4 Canada Canada Your file Votre référence ISBN: 0-612-93864-6 Our file Notre référence ISBN: 0-612-93864-6 The author has granted a non­ L'auteur a accordé une licence non exclusive licence allowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or sell reproduire, prêter, distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/film, de reproduction sur papier ou sur format électronique. The author retains ownership of theL'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts from it Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou aturement reproduits sans son permission. autorisation. In compliance with the Canadian Conformément à la loi canadienne Privacy Act some supporting sur la protection de la vie privée, forms may have been removed quelques formulaires secondaires from this dissertation.
    [Show full text]
  • Meridian and Interstitium
    Kuo and Liang, J Pharma Reports 2018, 3:2 Journal of Pharmacological Reports Mini Review Open Access Meridian and Interstitium Yu Cheng Kuo1* and Shih Hsuan Liang2 1Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taiwan 2Department of Radiology, Mackay Memorial Hospital, Taipei, Taiwan *Corresponding author: Yu-Cheng Kuo, Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taiwan, Tel: + 886-2- 27361661; E-mail: [email protected] Received date: May 10, 2018; Accepted date: May 30, 2018; Published date: June 06, 2018 Copyright: © 2018 Kuo YC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Meridian concept provides us an ideal and economic guide role to discover new drugs from herb and compounds. Through the harmonics of blood pressure pulse, we could quantitatively measure the meridian for physiological, pathological and pharmacological condition. Meridian concept reflexes the efficient design of radial resonance in Hemodynamic. However, the circulatory theory in Chinese Medicine is not only cardiovascular system, but also including the fluid recycle system. Keywords: Blood pressure; Chinese medicine; Cardiovascular harmonic arterial pulse wave propagation. The intracellular fluid, system; Circulatory system extracellular fluid in the interstitium resonances with arterial pressure pulse waves and moves periodically to exchange oxygen, nutrient Introduction efficiently. Wang et al. found that resonant arterial pressure pulse waves can be strengthen and transmitted in those meridians [10]. This Water is the essential element of life.
    [Show full text]
  • Interstitial Fluid Lung Disease (IFLD) of the Interstitium Organ the Cause and Self-Care to a Self- Cure for Lung Disease
    Authors: Robert O Young DSc. PhD. and Dr. Galina Migalko MD, NMD 16390 Dia del Sol, Valley Center, California 92082 Interstitial Fluid Lung Disease (IFLD) of the Interstitium Organ The Cause and Self-Care to a Self- Cure for Lung Disease Abstract Interstitial lung disease (IFLD), or diffuse parenchymal lung disease (DPLD),[3] is a group of lung diseases affecting the Interstitium (the interstitial fluids or space around the alveoli (air sacs of the lungs).[4] It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, and perivascular and perilymphatic tissues. It occurs when metabolic, dietary, respiratory and environmental acids injure the lung tissues that triggers an abnormal healing response. Ordinarily, the body generates just the right amount of tissue to repair acid damage, but in interstitial lung disease, the repair process goes awry because of the acidic pH (ideal healing takes place at a pH of 7.365) [5]) of the interstitial fluids that effects the normal healing of the tissue around the air sacs (alveoli) and therefore becomes scarred and thickened. Micrograph of usual interstitial pneumonia (UIP). UIP is the most common pattern of interstitial pneumonia (a type of interstitial lung disease) and usually represents pulmonary fibrosis caused by decompensated acidosis of the interstitial fluids of the largest organ of the human body - the Interstitium. H&E stain. Autopsy specimen. This makes it more difficult for oxygen to pass into the bloodstream. The term ILD is used to distinguish these diseases from obstructive airways diseases but the cause of all lung disease is due to decompensated acidosis of the interstitial fluids (pH is below 7.2) that is systemic although affecting the weakest area of the lungs.
    [Show full text]